The principal objective of this research plan is to demonstrate the effectiveness of a unique antigen delivery system for the induction of active immunity in mice against infection by Herpes simplex virus type 2 (HSV-2). The vaccine to be tested consists of an antigenic fusion protein formulated in an immunogenic liposome. The Specific Aims of this project are to: construct the liposomal-HSV-2 epitope vaccine; verify the immunogenicity of the vaccine design; and, demonstrate protective mucosal immunity to a lethal vaginal challenge by HSV-2. If successful, this novel vaccine technology should allow: (1) the commercial production of large quantities of purified immunogen using standard protein isolation techniques; (2) maximum flexibility for the insertion of single or multiple epitopes within a standard gene cassette for the rapid development of new vaccines; (3) easy incorporation of the antigen protein into immunogenic liposomes, resulting in a commercially viable process for large scale vaccine production; and (4) elimination of adverse side effects associated with the use of killed or modified live bacterial or viral vaccines. The choice of HSV-2 to demonstrate the utility of this design could have widespread implications for the treatment of all sexually transmitted diseases including HIV, the etiological agent of AIDS. PROPOSED COMMERCIAL APPLICATION: The potential commercial advantages of this vaccine and for any other vaccines developed using this approach include: a high margin of safety because the vaccine is non-pathogenic with minimal toxicity; relatively straightforward manufacturing procedures which make the process less costly; and efficacy comparable to virus-based vaccines. The proposed technology is also flexible; new vaccines can be made quickly and easily by simple "cutting and pasting" new antigen sequences at the proper sites in the expression vector. Given the ability to rapidly design and engineer new vaccines, the potential commercial applications for this technology range from pathogenic disease to cancers.